“Happy families are all alike; every unhappy family is unhappy in its own way.”

A few months back I was impressed with a paper that examined some serious chromosomal consequences that were possibly affecting cognitive development in some individuals. It struck me how important it was that something we haven’t had the tools to explore that effectively in the past–chromothripsis–was going to become more observed and better characterized. And it was going to offer at least some understanding in otherwise uncharacterized medical scenarios, which were hugely frustrating to affected families. These “genomic catastrophe” events might not be that common–but for the patients and their families, the effects are profound. And often unique. Recently “pulverized” chromosomes were also described in cancer cells. It’s hard to imagine how to fix massive restructurings of this sort.

Another article today talked about the search for more of the underlying features of mental disabilities and it reminded me of that: Gene hunt is on for mental disability. This involves taking more genome sequencing into clinical situations. The focus is exome sequencing so far, which is different from that other analysis I was intrigued by, and they have found a decent number of leads for many of the people they’ve examined with this strategy.

By comparing the children’s exomes with those of the parents, the researchers have identified new mutations — potential causes of the disorder — in as many as 40% of the cases. The other programmes are having similar success at making possible genetic diagnoses.

This is going to be good news and bad news. When they can identify the likely issue, there are going to be a lot of cases where there’s not much to be done at this time. It’s still important to know–and may offer the families answers they haven’t had–but will certainly continue to be frustrating that there’s no actions available. It’s going to be important knowledge, though, to drive future research which could eventually lead to treatments someday.

But some cases will be completely unique, probably–like in the chromothripsis situations. And some families may not have any answers at all. I’m glad to see the work is going on, though. And that the demise of whole genome explorations is rather unlikely at this point. There’s a lot we need to know–and there will be a lot of demand for this from people who want answers.


Liu, P., Erez, A., Nagamani, S., Dhar, S., Kołodziejska, K., Dharmadhikari, A., Cooper, M., Wiszniewska, J., Zhang, F., Withers, M., Bacino, C., Campos-Acevedo, L., Delgado, M., Freedenberg, D., Garnica, A., Grebe, T., Hernández-Almaguer, D., Immken, L., Lalani, S., McLean, S., Northrup, H., Scaglia, F., Strathearn, L., Trapane, P., Kang, S., Patel, A., Cheung, S., Hastings, P., Stankiewicz, P., Lupski, J., & Bi, W. (2011). Chromosome Catastrophes Involve Replication Mechanisms Generating Complex Genomic Rearrangements Cell, 146 (6), 889-903 DOI: 10.1016/j.cell.2011.07.042

Crasta, K., Ganem, N., Dagher, R., Lantermann, A., Ivanova, E., Pan, Y., Nezi, L., Protopopov, A., Chowdhury, D., & Pellman, D. (2012). DNA breaks and chromosome pulverization from errors in mitosis Nature, 482 (7383), 53-58 DOI: 10.1038/nature10802

Callaway, E. (2012). Gene hunt is on for mental disability Nature, 484 (7394), 302-303 DOI: 10.1038/484302a

Title quote from Anna Karenina, Tolstoy.